A novel nebulized drug delivery system based on an innovative high-pressure peristaltic pump availably applied to pressurized intraperitoneal aerosol chemotherapy.

Abstract

Background: Management of peritoneal carcinomatosis (PC) remains a significant clinical challenge due to a lack of effective therapies. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been identified as a safe and efficacious treatment for PC. However, despite the observed high potential for PIPAC in treating numerous PC cases, the technology is still limited in China. To address this deficit, we developed a novel nebulized drug delivery system (NDDS) and evaluated it in this study.

Methods: The NDDS was developed and was systematically assessed through tests of mechanical properties, granulometric analyses, sprayed distribution tests, and gravimetric analyses; moreover, drug penetration and distribution were examined in vitro and in a porcine model (female Tibetan pig).

Results: The NDDS, which included a high-pressure peristaltic pump, demonstrated a pressure initiation time of 5 s and a spray angle of 70°. Nebulization was consistent from the fifth second onward, with a median droplet diameter of 25.0-26.5 µm. The diameters of the sprayed intensive and expanded area were 26.1±1.4 and 48.5±1.0 cm at the vertical distance of 15 cm, and the stress generated was ≤3.790 Pa. Intraluminal drug distribution was extensive but heterogeneity, with 100- to 400-µm drug penetration depth (PD), and the optimal drug PD was observed in locations directly opposite to or adjacent surrounding the nozzle.

Conclusions: The developed NDDS demonstrated promising mechanical properties, effective granulometric characteristics, extensive spray coverage, and satisfactory drug penetration and distribution. It offers a practicable solution for the application of PIPAC and will hopefully improve the current dilemma in PC therapy.